This invention is generally in the field of polymer blends, interpenetrating networks (IPN) of polymers, and semi-interpenetrating networks (semi-IPNs) of polymers, specifically those including polyphosphazene, for use in controlled degradation applications, such as biomedical applications.
The ability to regulate the rate and extent of degradation of a material is critical in many environmental and biomedical applications. In recent years, major research efforts have been directed towards the development of biodegradable materials for biomedical applications such as controlled drug delivery and tissue regeneration. The field of controlled drug delivery has evolved in an effort to overcome the many limitations of traditional drug delivery. Conventional parenteral drug delivery relies on repeated injection or infusion via different routes to achieve tissue levels of desired drugs. Consequently, patient compliance can be unsatisfactory. Waldvogel, in Orthopaedic Infection, Springer-Verlag: New York (1988) pp. 1-8. In addition, repeated injection or infusion leads to high serum levels of the drug, thus posing serious toxicity risks to otherwise healthy organ systems. Furthermore, wastage and costs can be considerable, because a substantial amount of the drug does not reach the target site.
By the 1950's technology had developed to successfully administer drugs at controlled rates using polymeric devices as the drug carriers. Laurencin and Langer, Clinics in Lab. Med. 7:301 (1987). Biodegradable, biocompatible matrices for controlled drug delivery provide many benefits. First, patient compliance is enhanced due to less frequent drug administration. Second, the risk of drug concentrations reaching toxic levels is minimized since the drug is released at controlled rates. Third, the cost of treatment is considerably reduced, because a smaller amount of drug can be used. Finally, in cases where the delivery device is surgically implanted, the need for a second surgical procedure in order to remove the drug-depleted device is obviated.
While biodegradable polymers, such as poly(lactide-co-glycolide) (PLGA), are useful in drug delivery and tissue regeneration applications since they degrade into harmless substances, drawbacks--primarily that they degrade by bulk erosion--limit their application. These polymers do not allow for release of a substance as controllable as is desired in certain controlled drug delivery applications. Since polymers of lactic and glycolic acids and their copolymers (PLGA) degrade quickly in the body into non-toxic products, PLGA is used for biodegradable sutures and can potentially be used in implantable screws, intravascular stents, pins, drug delivery devices, and as a temporary scaffold for tissue and bone repair. Additionally, PLGA has good mechanical properties which improve the structural integrity of such devices. However, since PLGA degrades completely by bulk erosion, it loses more than 50% of its mechanical strength in less than two months, which can lead to uncontrollable release rates of drugs and can develop biocompatibility problems (probably due to an accumulation of lactic and glycolic acids during degradation).
Other applications are also dependent on the rate and extent of degradation. For example, plastic medical devices, food containers, bottles, bags, and other materials currently in use create an extensive, expensive waste disposal problem. It is therefore highly desirable to create biodegradable materials that retain sufficient mechanical strength over the desired time period, but which degrade when no longer useful.
Accordingly, it is an object of this invention to provide biodegradable polymer mixtures for use in biomedical and environmental applications.
It is another object of this invention to provide biodegradable polymeric matrices which degrade by surface erosion.
It is another object of this invention to provide biodegradable polymeric matrices for which one can modulate the degradation rate.
It is another object of this invention to provide biodegradable polymeric matrices with a sufficient degree of flexibility to facilitate molding of the polymeric matrix.
It is another object of this invention to provide biodegradable, biocompatible polymeric matrices for controlled drug delivery and bone repair applications.
It is another object of this invention to provide biodegradable, biocompatible polymeric matrices with good osteoconductivity to aid in drug delivery to sites within bone.
It is another object of this invention to provide biodegradable polymeric matrices which degrade by bulk erosion for environmental uses.